OBJECTIVE: This study aims to determine if the presence of specific clinical and computed tomography (CT) patterns are associated with epidermal growth factor receptor (EGFR) mutation in patients with non-small cell lung cancer.
METHODS: A systematic literature review and meta-analysis was carried out in 6 databases between January 2002 and July 2021. The relationship between clinical and CT patterns to detect EGFR mutation was measured and pooled using odds ratios (OR). These results were used to build several mathematical models to predict EGFR mutation.
RESULTS: 34 retrospective diagnostic accuracy studies met the inclusion and exclusion criteria. The results showed that ground-glass opacities (GGO) have an OR of 1.86 (95%CI 1.34 -2.57), air bronchogram OR 1.60 (95%CI 1.38 - 1.85), vascular convergence OR 1.39 (95%CI 1.12 - 1.74), pleural retraction OR 1.99 (95%CI 1.72 - 2.31), spiculation OR 1.42 (95%CI 1.19 - 1.70), cavitation OR 0.70 (95%CI 0.57 - 0.86), early disease stage OR 1.58 (95%CI 1.14 - 2.18), non-smoker status OR 2.79 (95%CI 2.34 - 3.31), female gender OR 2.33 (95%CI 1.97 - 2.75). A mathematical model was built, including all clinical and CT patterns assessed, showing an area under the curve (AUC) of 0.81.
CONCLUSIONS: GGO, air bronchogram, vascular convergence, pleural retraction, spiculated margins, early disease stage, female gender, and non-smoking status are significant risk factors for EGFR mutation. At the same time, cavitation is a protective factor for EGFR mutation. The mathematical model built acts as a good predictor for EGFR mutation in patients with lung adenocarcinoma.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

UNASSIGNED: To demonstrate semantic, radiomics, and the combined risk models related to the prognoses of pulmonary pleomorphic carcinomas (PCs).
UNASSIGNED: We included 85 patients (M:F = 71:14; age, 35-88 [mean, 63 years]) whose imaging features were divided into training (n = 60) and test (n = 25) sets. Nineteen semantic and 142 radiomics features related to tumors were computed. Semantic risk score (SRS) model was built using the Cox-least absolute shrinkage and selection operator (LASSO) approach. Radiomics risk score (RRS) from CT and PET features and combined risk score (CRS) adopting both semantic and radiomics features were also constructed. Risk groups were stratified by the median of the risk scores of the training set. Survival analysis was conducted with the Kaplan-Meier plots.
UNASSIGNED: Of 85 PCs, adenocarcinoma was the most common epithelial component found in 63 (73 %) tumors. In SRS model, four features were stratified into high- and low-risk groups (HR, 4.119; concordance index ([C-index], 0.664) in the test set. In RRS model, five features helped improve the stratification (HR, 3.716; C-index, 0.591) and in CRS model, three features helped perform the best stratification (HR, 4.795; C-index, 0.617). The two significant features of CRS models were the SUVmax and the histogram feature of energy ([CT Firstorder Energy]).
UNASSIGNED: In PCs of the lungs, the combined model leveraging semantic and radiomics features provides a better prognosis compared to using semantic and radiomics features separately. The high SUVmax of solid portion (CT Firstorder Energy) of tumors is associated with poor prognosis in lung PCs.

Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.

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Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.

Oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. Several viruses have undergone evaluation in clinical trials in the last decades, and the first agent is about to be approved to be used as a novel cancer therapy modality. In the current review, an overview is presented on recent (pre)clinical developments in the field of oncolytic viruses that have previously been or currently are being evaluated in clinical trials. Special attention is given to possible safety issues like toxicity, environmental shedding, mutation and reversion to wildtype virus.